Effects of surgery on microvascular function in venous insufficiency.

BACKGROUND: The aim of our study was to assess the effects of venous stripping on microvascular functions in isolated great saphenous vein insufficiency. METHODS: Two groups of participants were prospectively evaluated. The first group included 15 healthy participants without any evidence of venous insufficiency. The second group included 20 patients with varicose veins because of great saphenous vein insufficiency. The demographics, venous clinical severity scores, and CEAP classifications of the patients were recorded. Next, all individuals underwent evaluations for microvascular vasoreactivity using an iontophoretic laser Doppler imager, and the outcomes were recorded. Patients with varicose veins underwent stripping surgeries, and microvascular vasoreactivity evaluations were repeated 6 weeks postoperatively. RESULTS: There was a statistically significant decrease in the patients with varicose veins compared with the control group in response to nitroprusside (SNP) applied at 4 mC in the supine position. Furthermore, there was also a significant difference in the response to acetylcholine (ACh) in patient group in the sitting position (P < 0.05). We also observed a statistically significant decrease in the responses to SNP applied for 1, 2, and 4 mC (P < 0.05) in the patients in the sitting position. The relief of pain and edema after surgery was found to be significant (P < 0,001). In the subgroup in which ACh was applied for 1 and 4 mC in the supine position, postoperative microvascular flow was significantly increased (P < 0.005). Moreover, based on the measurements taken in the supine position, the patients in the subgroup in which SNP was applied for 1, 2, or 4 mC exhibited significantly increased postoperative microvascular dilatation (P < 0.005). CONCLUSIONS: Saphenous vein insufficiency impairs the endothelium-dependent vasodilatation response in the perimalleolar region, and partial recoveries in microvascular function were observed after surgical treatment.

Augmentation of ADAMTS9 gene expression by IL-1ß is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor-κB (NF-κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF-κB in IL-1ß-induced ADAMTS9 expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1ß. They were pretreated with 20 µM PD98059 (specific inhibitor of p44/42 kinase), 10 µM SB203580 (specific inhibitor of p38 kinase), 20 µM SB600125 (MAPK inhibitor), and 1 µM Wortmannin and 10 µM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL-1ß. For the effects of NF-κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL-1ß. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real-time polymerase chain reaction (PCR) was performed on cDNA samples. There was a significant difference between control and stimulated cells in terms of ADAMTS9/ß-actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-κB inhibitors, led to a decrease in the ratio of ADAMTS9/ß-actin. As a conclusion, the pathways MAPK and NF-κB were thought to be responsible pathways for the induction of ADAMTS9 gene.